Md2topical Tretinoin 0.05% Enhances Angiogenesis in Full-Thickness Wounds in Rats:a Comparative Study of Single and Repeated Application in Rats

Background: Angiogenesis plays a crucial role in the proliferative phase of wound healing by supplying oxygen and nutrients to regenerating tissue. Vascular Endothelial Growth Factor (VEGF) is the key mediator in this process. Tretinoin, a vitamin A derivative commonly used in dermatology, may influence angiogenesis in a dose- and contextdependent manner, but its role in acute wound models remains underexplored. Methods: This experimental study involved 27 male Rattus norvegicus (Wistar strain), randomized into three groups (n=9): control (no tretinoin), single-dose topical tretinoin 0.05%, and repeated-dose for four consecutive days. Fullthickness excisional wounds (20 mm diameter) were created on the dorsal skin. On day five, tissue samples were collected. Neovascular density was assessed using hematoxylin-eosin staining with a semi-quantitative 0–4 scale, while VEGF expression was measured via immunohistochemistry using digital quantification. Results: Repeated tretinoin application significantly increased neovascular density (mean score 2.67) and VEGF expression (72.54 ± 15.72) compared to single-dose (1.67; 30.42 ± 15.52) and control groups (1.1; 11.07 ± 2.89). Statistical analysis confirmed significant differences among all groups (p < 0.05) using Kruskal-Wallis and ANOVA, with post hoc tests showing consistent intergroup significance. Conclusion: Topical tretinoin 0.05% enhances angiogenesis in full-thickness wounds, with repeated application producing greater effects. These findings support its potential use as a pro-angiogenic agent in acute wound management.